How does social media use influence the mental health of pancreatic cancer patients: a chain mediating effect of online social support and psychological resilience.

Background: Pancreatic cancer is an extremely malignant disease that poses a serious threat to the mental health of patients. Many cancer patients now use social media for online social support. However, the impact of social media on mental health is currently inconsistent in the academic community. Therefore, this study aimed to examine the mediating effects of online social support and psychological resilience in the relationship between social media use and mental health of pancreatic cancer patients. Methods: Four hundred and twenty-five valid questionnaires were collected through convenience sampling. All data were processed using SPSS 26.0 and AMOS 26.0. We examine the influence relationships among latent variables by constructing a structural equation model. Then SPSS Process Macro was used to test the chain mediating effect of the model. Results: The results showed that (1) anxiety situations occurred in 22.2% of participants (N = 94), while the incidence of depression was 20.2% (N = 86). (2) Social media use positively influenced online social support (ß = 0.990, p < 0.001), psychological resilience (ß = 0.504, p < 0.001), and mental health (ß = 0.330, p < 0.001); online social support positively influenced psychological resilience (ß = 0.535, p < 0.001) and mental health (ß = 0.354, p < 0.001); psychological resilience significantly and positively influenced mental health (ß = 0.243, p < 0.001). (3) The chain mediating effect of online social support and psychological resilience was significant at 0.253 with a confidence interval of [0.178, 0.340]. Conclusion: Pancreatic cancer patients in China are exposed to a high burden of anxiety and depression, which requires urgent attention. Meanwhile, online social support and psychological resilience played a chain mediating role between social media use and mental health (anxiety and depression), and our results provide new insights and ways to support the mental health improvement of pancreatic cancer patients.

Actinobacillus pleuropneumoniae FliY and YdjN are involved in cysteine/cystine utilization, oxidative resistance, and biofilm formation but are not determinants of virulence.

Introduction: Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is a member of Actinobacillus in family Pasteurellaceae. It is the causative agent of porcine pleuropneumonia, which has caused huge economic losses to pig industry over the world. Cysteine is a precursor of many important biomolecules and defense compounds in the cell. However, molecular mechanisms of cysteine transport in A. pleuropneumoniae are unclear. Methods: In this study, gene-deleted mutants were generated and investigated, to reveal the roles of potential cysteine/cystine transport proteins FliY and YdjN of A. pleuropneumoniae. Results: Our results indicated that the growth of A. pleuropneumoniae was not affected after fliY or ydjN single gene deletion, but absence of both FliY and YdjN decreased the growth ability significantly, when cultured in the chemically defined medium (CDM) supplemented with cysteine or cystine as the only sulfur source. A. pleuropneumoniae double deletion mutant ΔfliYΔydjN showed increased sensitivity to oxidative stress. Besides, trans-complementation of YdjN into ΔfliYΔydjN and wild type leads to increased biofilm formation in CDM. However, the virulence of ΔfliYΔydjN was not attenuated in mice or pigs. Discussion: These findings suggest that A. pleuropneumoniae FliY and YdjN are involved in the cysteine/cystine acquisition, oxidative tolerance, and biofilm formation, but not contribute to the pathogenicity of A. pleuropneumoniae.

Activation of ROS-PERK-TFEB by filbertone ameliorates neurodegenerative diseases via enhancing the autophagy-lysosomal pathway.

The molecular mechanisms underlying the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease (PD), and Huntington's disease remain enigmatic, resulting in an unmet need for therapeutics development. Here, we suggest that filbertone, a key flavor compound found in the fruits of hazel trees of the genus Corylus, can ameliorate PD via lowering the abundance of aggregated α-synuclein. We previously reported that inhibition of hypothalamic inflammation by filbertone is mediated by suppression of nuclear factor kappa-B. Here, we report that filbertone activates PERK through mitochondrial reactive oxygen species production, resulting in the increased nuclear translocation of transcription factor-EB in SH-SY5Y human neuroblastoma cells. TFEB activation by filbertone promotes the autophagy-lysosomal pathway, which in turn alleviates the accumulation of α-synuclein. We also demonstrate that filbertone prevented the loss of dopaminergic neurons in the substantia nigra and striatum of mice on high-fat diet. Filbertone treatment also reduced high-fat diet-induced α-synuclein accumulation through upregulation of the autophagy-lysosomal pathway. In addition, filbertone improved behavioral abnormalities (i.e., latency time to fall and decrease of running distance) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD murine model. In conclusion, filbertone may show promise as a potential therapeutic for neurodegenerative disease.

Hypoxia signaling in human health and diseases: implications and prospects for therapeutics.

Molecular oxygen (O2) is essential for most biological reactions in mammalian cells. When the intracellular oxygen content decreases, it is called hypoxia. The process of hypoxia is linked to several biological processes, including pathogenic microbe infection, metabolic adaptation, cancer, acute and chronic diseases, and other stress responses. The mechanism underlying cells respond to oxygen changes to mediate subsequent signal response is the central question during hypoxia. Hypoxia-inducible factors (HIFs) sense hypoxia to regulate the expressions of a series of downstream genes expression, which participate in multiple processes including cell metabolism, cell growth/death, cell proliferation, glycolysis, immune response, microbe infection, tumorigenesis, and metastasis. Importantly, hypoxia signaling also interacts with other cellular pathways, such as phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-B (NF-κB) pathway, extracellular signal-regulated kinases (ERK) signaling, and endoplasmic reticulum (ER) stress. This paper systematically reviews the mechanisms of hypoxia signaling activation, the control of HIF signaling, and the function of HIF signaling in human health and diseases. In addition, the therapeutic targets involved in HIF signaling to balance health and diseases are summarized and highlighted, which would provide novel strategies for the design and development of therapeutic drugs.

PERK activation by SB202190 ameliorates amyloidogenesis via the TFEB-induced autophagy-lysosomal pathway.

The protein kinase R (PKR)-like endoplasmic reticulum (ER) kinase (PERK), a key ER stress sensor of the unfolded protein response (UPR), can confer beneficial effects by facilitating the removal of cytosolic aggregates through the autophagy-lysosome pathway (ALP). In neurodegenerative diseases, the ALP ameliorates the accumulation of intracellular protein aggregates in the brain. Transcription factor-EB (TFEB), a master regulator of the ALP, positively regulates key genes involved in the cellular degradative pathway. However, in neurons, the role of PERK activation in mitigating amyloidogenesis by ALP remains unclear. In this study, we found that SB202190 selectively activates PERK independently of its inhibition of p38 mitogen-activated protein kinase, but not inositol-requiring transmembrane kinase/endoribonuclease-1α (IRE1α) or activating transcription factor 6 (ATF6), in human neuroblastoma cells. PERK activation by SB202190 was dependent on mitochondrial ROS production and promoted Ca2+-calcineurin activation. The activation of the PERK-Ca2+-calcineurin axis by SB202190 positively affects TFEB activity to increase ALP in neuroblastoma cells. Collectively, our study reveals a novel physiological mechanism underlying ALP activation, dependent on PERK activation, for ameliorating amyloidogenesis in neurodegenerative diseases.

The impact of exposure to HPV related information and injunctive norms on young women's intentions to receive the HPV vaccine in China: A structural equation model based on KAP theory.

Background: The HPV vaccination is a crucial line of defensing against cervical cancer. As a result of government support and positive publicity from the majority of media, a craze for HPV vaccination has occurred in China. Besides, the intentions to get the HPV vaccine among women of appropriate age is also influenced by families' and friends' attitudes and perceptions toward HPV vaccine. Therefore, the purpose of this study was to investigate how HPV related information exposure and injunctive norms affect young Chinese women's intentions to receive the HPV vaccine. Methods: A structural equation model was developed based on KAP theory, and 567 effective questionnaires were collected through an online survey. We used SPSS 26.0 for the reliability and validity analysis and the differential testing of demographic characteristics, and Amos 26.0 for the goodness-of-fit analysis and paths testing of the model. Results: Our findings showed that (1) intention to receive HPV vaccine differed significantly in age (P = 0.046), educational background (P = 0.001), and occupation (P = 0.004). (2) Exposure to HPV related information positively affected knowledge about HPV (ß = 0.316, P < 0.001) and intention to receive HPV vaccine (ß = 0.141, P < 0.001). (3) Knowledge about HPV positively affected attitude toward HPV vaccine (ß=0.341, P < 0.001), but negatively affected intention to receive HPV vaccine (ß = -0.148, P < 0.05), and attitude toward HPV vaccine positively affected intention to receive HPV vaccine (ß = 0.594, P < 0.001). (4) Injunctive norms positively affected attitude toward HPV vaccine (ß = 0.362, P < 0.001) and intention to receive HPV vaccine (ß = 0.420, P < 0.001). Conclusions: Exposure to HPV related information influenced young Chinese women's intentions to receive the HPV vaccine and related knowledge, that is, the more frequently they were exposed to HPV related information, the stronger their intentions to receive the vaccine and the higher their HPV knowledge. Also, the perception and support of HPV vaccination by people around them will further influence their attitudes and intentions to receive the HPV vaccine.

A novel recurrence associated immune gene signature and its clinical significance in liver cancer.

Hepatocellular carcinoma (HCC) is one of the most common malignancies across nations. Although the outcome of HCC has been improved significantly with the advances in comprehensive treatment, patients remain suffered from recurrence as well as metastasis. Therefore, it is urgent to identify reliable biomarkers for predicting the recurrence of HCC, by which the treating strategy can be made to restrain tumor progress. Increasing evidence has shown the association between immune signature and prognosis of HCC. Thus, we aimed to discover an immune-related gene signature that can estimate the recurrence rates of HCC. We collected gene expression profiles and clinical information of patients from GEO and TCGA dataset. Furthermore, we conducted a lasso regression analysis and established a recurrence-related model consisting of 36 immune-related gene pairs (IRGPs) with 54 genes. We validated the IRGPs in the validation cohort and observed that the immune-related signature robustly stratified patients with HCC into high- and low-risk groups in terms of recurrence (P < 0.001). Multivariant Cox regression analysis showed the relationship between the model and recurrence outcomes (Hazard Ratio: 3.81 95% Confidence Interval: 2.90-5.00). Gene Ontology and KEGG enrichment analyses revealed that those genes were enriched in important signaling pathways. In summary, we developed a robust model based on the signature of immune-related genes for forecasting the recurrence outcome of patients with HCC, which holds the potential to assist clinical practice.

Synthetic Evaluation of MicroRNA-1-3p Expression in Head and Neck Squamous Cell Carcinoma Based on Microarray Chips and MicroRNA Sequencing.

BACKGROUND: MicroRNA-1-3p (miR-1-3p) exerts significant regulation in various tumor cells, but its molecular mechanisms in head and neck squamous cell carcinoma (HNSCC) are still ill defined. This study is aimed at detecting the expression of miR-1-3p in HNSCC and at determining its significant regulatory pathways. METHODS: Data were obtained from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Oncomine, ArrayExpress, Sequence Read Archive (SRA) databases, and additional literature. Expression values of miR-1-3p in HNSCC were analyzed comprehensively. The R language software was employed to screen differentially expressed genes, and bioinformatics assessment was performed. One sequence dataset (HNSCC: n = 484; noncancer: n = 44) and 18 chip datasets (HNSCC: n = 656; noncancer: n = 199) were obtained. RESULTS: The expression of miR-1-3p in HNSCC was visibly decreased in compare with noncancerous tissues. There were distinct differences in tumor state (P = 0.0417), pathological stage (P = 0.0058), and T stage (P = 0.0044). Comprehensive analysis of sequence and chip data also indicated that miR-1-3p was lowly expressed in HNSCC. The diagnostic performance of miR-1-3p in HNSCC is reflected in the sensitivity and specificity of the collection, etc. Bioinformatics analysis showed the possible biological process, cellular component, molecular function, and KEGG pathways of miR-1-3p in HNSCC. And ITGB4 was a possible target of miR-1-3p. CONCLUSIONS: miR-1-3p's low expression may facilitate tumorigenesis and evolution in HNSCC through signaling pathways. ITGB4 may be a key gene in targeting pathways but still needs verification through in vitro experiments.

PLG inhibits Hippo signaling pathway through SRC in the hepatitis B virus-induced hepatocellular-carcinoma progression.

PURPOSE: Hepatitis B virus (HBV) infection is one main cause of hepatocellular carcinoma (HCC), but the mechanisms of pathogenesis still remain unclear. METHODS: We screened the 1351 differentially expressed genes related to HBV-induced HCC by bioinformatics analysis from databases and found that Plasminogen (PLG) may be a key gene in HBV-induced HCC progression. Then, we used a series of experiments in vivo and in vitro to explore the roles of PLG in HBV-HCC progression, such as qRT-PCR, western blot, ELISA, flow cytometry and TUNEL assay, subcutaneous xenografts and histopathological analysis to reveal the underlying mechanisms. RESULTS: PLG was over-expressed in HBV positive hepatocellular carcinoma tissues and cells. PLG silencing promoted HBV-HCC cell apoptosis in vitro and suppressed the growth of HBV-induced HCC xenografts in vivo both through inhibiting HBV replication. Then, GO and KEGG analysis of these differentially expressed genes revealed that the Hippo pathway was the key pathway involved in HBV-induced HCC, and SRC, a downstream target gene of PLG, was highly expressed in HBV-induced HCC and related to the Hippo pathway. Thus, we speculated that PLG promoted HBV-induced HCC progression through up-regulating and activating the expression of SRC and promoting Hippo signaling pathway function on HBV-HCC cell survival. CONCLUSION: Our study suggests PLG may be an activator of HBV-infected hepatocellular carcinoma development, as a novel prognostic biomarker and therapeutic target for HBV-HCC.

GSK-3ß inhibition by curcumin mitigates amyloidogenesis via TFEB activation and anti-oxidative activity in human neuroblastoma cells.

The translocation of transcription factor EB (TFEB) to the nucleus plays a pivotal role in the regulation of basic cellular processes, such as lysosome biogenesis and autophagy. Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome, which is important in maintaining cellular homeostasis during environmental stress. Furthermore, oxidative stress is a critical cause for the progression of neurodegenerative diseases. Curcumin has anti-oxidative and anti-inflammatory activities, and is expected to have potential therapeutic effects in various diseases. In this study, we demonstrated that curcumin regulated TFEB export signalling via inhibition of glycogen synthase kinase-3ß (GSK-3ß); GSK-3ß was inactivated by curcumin, leading to reduced phosphorylation of TFEB. We further showed that H2O2-induced oxidative stress was reduced by curcumin via the Nrf2/HO-1 pathway in human neuroblastoma cells. In addition, we showed that curcumin induced the degradation of amyloidogenic proteins, including amyloid-ß precursor protein and α-synuclein, through the TFEB-autophagy/lysosomal pathway. In conclusion, curcumin regulates autophagy by controlling TFEB through the inhibition of GSK-3ß, and increases antioxidant gene expression in human neuroblastoma cells. These results contribute to the development of novel cellular therapies for neurodegenerative diseases.

DTNA promotes HBV-induced hepatocellular carcinoma progression by activating STAT3 and regulating TGFß1 and P53 signaling.

OBJECTIVE: Hepatitis B virus (HBV) infection causes liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC) development, but the underlying mechanism remains poorly understood. This study aimed to investigate the roles and molecular mechanisms of Dystrobrevin-α (DTNA) in HBV-induced liver cirrhosis and HCC pathogenesis. METHODS: DTNA expression was bioinformatically analyzed using the GEO database. DTNA expression was silenced by transfection with shRNAs. Cell proliferation and apoptosis were evaluated by MTT and flow cytometry respectively. The expression of genes in mRNA or protein levels was assessed by quantitative RT-PCR and western blotting. The interaction between proteins was predicted with the String and GCBI online softwares, and then confirmed by co-immunoprecipitation. Animal models were established by injecting nude mice with AVV8-HBV1.3 vector. RESULTS: Bioinformatics analysis showed a significantly increase in DTNA expression in HBV-positive liver cirrhosis and HCC patients. HBV infection caused a significantly increase in DTNA expression in HCC cell lines HepAD38 and HepG2.2.15. DTNA knockdown suppressed proliferation and promoted apoptosis of HBV-infected HepAD38 and HepG2.2.15 cells. HBV induced elevated expression of fibrosis-related genes Collagen II and TGFß1 in LO-2 cells, which were suppressed by DTNA knockdown. DTNA directly binded with STAT3 protein to promote STAT3 phosphorylation and TGFß1 expression and repress P53 expression in HBV-infected HepAD38 and LO-2 cells. The DTNA/STAT3 axis was activated during HBV-induced fibrosis, cirrhosis and HCC development in mouse model. CONCLUSION: DTNA binds with and further activates STAT3 to induce TGFß1 expression and repress P53 expression, thus promoting HBV-induced liver fibrosis, cirrhosis and hepatocellular carcinoma progression.

FGD1 exhibits oncogenic properties in hepatocellular carcinoma through regulating cell morphology, autophagy and mitochondrial function.

Faciogenital Dysplasia 1 (FGD1) has been involved in a variety of biological processes, including cytoskeleton restructuring, cell morphology, cell cycle progression, and cell polarity. Abnormal expression of FGD1 was also identified in several types of cancers, indicating its critical role in the development of cancers. However, little is known about the role of FGD1 in hepatocellular carcinoma (HCC). In this study, the expression of FGD1 in HCC was mined with the RNA sequencing data from the cancer genome atlas. By over-expressing or knocking down of FGD1, the effects of FGD1 on the malignant behavior of HCC were evaluated both in vitro and in vivo. We find that FGD1 is up-regulated in HCC and correlated with the development and prognosis of HCC. By over-expressing or knocking down of FGD1, the effects of FGD1 on the malignant behavior of HCC were evaluated both in vitro and in vivo. Knockdown of FGD1 remarkably inhibits the malignant behaviors and causes morphological disorder of pseudopodia, autophagy inhibition and mitochondrial dyfunction in HCC cells. Further investigation shows that Cdc42, a Rho GTPase, plays a role in these processes. Overexpression of FGD1 significantly promotes the oncogenic properties of HCC cells. Collectively, these findings reveal that FGD1 exhibits oncogenic properties in HCC through regulating cell morphology, autophagy and mitochondrial function, suggesting that FGD1 may serve as a potential therapeutic target for HCC.

TRAIP promotes malignant behaviors and correlates with poor prognosis in liver cancer.

TRAF-interacting protein (TRAIP) is a RING-type E3 ubiquitin ligase which has been implicated in various cellular processes, including NF-κB activation, DNA damage response, mitosis, and tumorigenesis. It is considered as a tumor suppressor in basal cell carcinomas and breast cancer in previous studies. However, in our current study, we found that TRAIP exhibited oncogenic properties in liver cancer. In order to determine its effect on tumor biology and the potential mechanism, a variety of advanced experimental technology was used, such as bioinformatic analysis, isobaric tags for relative and absolute quantification (iTRAQ) analysis, tissue microarray detection, and other in vitro cell biology experiments. The results showed that TRAIP was up-regulated in liver cancer and negatively correlated with prognosis. When TRAIP was knocked-down with lentivirus containing specific targeting short hairpin RNAs, the malignant behaviors of Bel7404 cells were significantly inhibited. Meanwhile, overexpression of TRAIP exerted oncogenic effects in SNU449 cells. More importantly, the iTRAQ analysis indicated that TRAIP was significantly related to centriole, centromere, and histone deacetylation, which are critical for mitosis. These findings are in line with previous reports that TRAIP contributes to proper mitosis. Additionally, the iTRAQ analysis also supported that TRAIP may affect G1/S transition by regulating the expression of certain cell cycle related proteins. In summary, our study firstly revealed that TRAIP was up-regulated and negatively correlated with prognosis in liver cancer patients and exhibited oncogenic properties in liver cancer cells, making it a potential target for treatment of liver cancer.

Machine Learning-Assisted System for Thyroid Nodule Diagnosis.

Background: Ultrasound (US) examination is helpful in the differential diagnosis of thyroid nodules (malignant vs. benign), but its accuracy relies heavily on examiner experience. Therefore, the aim of this study was to develop a less subjective diagnostic model aided by machine learning. Methods: A total of 2064 thyroid nodules (2032 patients, 695 male; Mage = 45.25 ± 13.49 years) met all of the following inclusion criteria: (i) hemi- or total thyroidectomy, (ii) maximum nodule diameter 2.5 cm, (iii) examination by conventional US and real-time elastography within one month before surgery, and (iv) no previous thyroid surgery or percutaneous thermotherapy. Models were developed using 60% of randomly selected samples based on nine commonly used algorithms, and validated using the remaining 40% of cases. All models function with a validation data set that has a pretest probability of malignancy of 10%. The models were refined with machine learning that consisted of 1000 repetitions of derivatization and validation, and compared to diagnosis by an experienced radiologist. Sensitivity, specificity, accuracy, and area under the curve (AUC) were calculated. Results: A random forest algorithm led to the best diagnostic model, which performed better than radiologist diagnosis based on conventional US only (AUC = 0.924 [confidence interval (CI) 0.895-0.953] vs. 0.834 [CI 0.815-0.853]) and based on both conventional US and real-time elastography (AUC = 0.938 [CI 0.914-0.961] vs. 0.843 [CI 0.829-0.857]). Conclusions: Machine-learning algorithms based on US examinations, particularly the random forest classifier, may diagnose malignant thyroid nodules better than radiologists.

Intensity-modulated radiotherapy combined with iodine-125 seed implantation in non-central recurrence of cervical cancer: A case report and literature review.

Recurrent cervical cancer is a clinically complex disease that is difficult to treat. There are numerous treatment options, but the results achieved by each are poor. External-beam radiation therapy of the pelvic lymph drainage area, in combination with intracavitary afterloading or the interstitial implantation of a radiation source (i.e., brachytherapy), are the current standard radiotherapy regimens used in high-risk clinical targets. However, there are few reports concerning the use of iodine-125 (125I) seed implantation brachytherapy in recurrent cervical cancer, and the effects of treatment and adverse reactions have not yet been systematically evaluated. In the present study one such case is reported, in which the patient was successfully treated with intensity-modulated radiotherapy (IMRT) in combination with 125I seed implantation. The patient, a 47-year-old woman, was initially diagnosed with International Federation of Gynecology and Obstetrics stage IB1 cervical cancer, and received a radical hysterectomy, left lateral adnexectomy and pelvic lymph node dissection. A follow-up examination 23 months later revealed vaginal invasion and a solitary lump in the cervical stump with a maximum diameter of 38 mm. The patient was subsequently diagnosed with recurrent cervical cancer and was treated with six cycles of docetaxel and nedaplatin chemotherapy, alongside IMRT and interstitial 125I seed implantation. At the point of manuscript submission, the patient's progression-free survival time was 33 months and long-term adverse reactions were acceptable. The response of this patient indicates that 125I seed implantation could be used as a complementary treatment for recurrent cervical cancer and may also prove to be a reliable means for the comprehensive treatment of primary cervical cancer, as the patient had characteristics similar to primary cervical cancer, although this hypothesis could not be confirmed in the present study.

Response of mouse thymic cells to radiation after transfusion of mesenchymal stem cells.

Thymic lymphoma is a highly invasive and even metastatic cancer. This study investigated the effects of mesenchymal stem cells (MSCs) transfusion on cell cycle, cell proliferation, CD3 expression, mutation frequency of T cell receptor using mouse model of thymic lymphoma.C57BL/6J young mouse models of thymoma were injected with MSCs. Six months later, the thymus was taken for pathological examination and flow cytometry studies. The cells were labeled with anti-CD4, CD8, CD3, propidium iodide, or CFDA-SE, cell cycle, proliferation kinetics, and mutation frequency of T cell receptor, respectively.Pathologic results showed that control had clear corticomedular structure with regularly shaped lymphocytes. After radiation, the thymus structure was completely destroyed, with lymphoid tumor cells diffusely distributed and heavily stained, and large nuclei. Transfusion of MSCs resulted in normal thymus structure. Cytometry studies showed that there were more CD4-/CD8- T cells in the thymus of irradiated mice than in control; transfusion of MSCs led to reduced CD4-/CD8- T cells. In irradiated mice, there were less CD4+/CD8+ T cells than in control and MSCs transfusion groups. It was observed that there were more cells arrested in G1 phase in the thymus cells and CD4-/CD8- T cells in irradiated mice than in other 2 groups, whereas there were more cells arrested in S phase in CD4+/CD8+ and CD4+/CD8- T cells in irradiated mice than in the other mice. In the thymus cells, and CD4+/CD8+ and CD4+/CD8- T cells, irradiated mice group had significantly less parent, G2, G3, and G4 cells, and more cells at higher generations, and also higher proliferation index. In CD4-/CD8- T cells, irradiated mice had significantly more parent, G2, and G3 cells, and less G4, G5, G6, and propidium iodide, as compared with the other 2 groups. The expression of CD3 in CD4/CD8 T cells was significantly higher than in control. MSCs transfusion improved CD3 expression, but was still less than the control. Irradiation resulted in very high mutation frequency of T cell receptor, which was barely affected by MSCs transfusion.Mesenchymal stem cell transfusion is able to restore the cell cycle and cell proliferation, but not CD3 expression and mutation frequency of T cell receptor in irradiated mice to control level.

Increased expression of kindlin-2 is correlated with hematogenous metastasis and poor prognosis in patients with clear cell renal cell carcinoma.

Kindlin-2 is involved in activating the integrin signaling pathway which plays an important role in regulating cancer cell invasion. However, the role of kindlin-2 may vary among cancer types. The aim of this study was to explore the possible association between kindlin-2 and clear cell renal cell carcinoma (ccRCC), and its potential role in the prognosis of ccRCC. Immunohistochemistry assays were used to examine kindlin-2 expression levels in cancer tissues obtained from 336 patients with ccRCC. The correlation between kindlin-2 expression levels and pathologic variables was then analyzed. In addition, the association between kindlin-2 expression levels and survival time was analyzed by Kaplan-Meier survival curves and log-rank tests. Of 336 ccRCC patients, 199 had high levels of kindlin-2 expression, while 137 had low kindlin-2 expression levels. Patients at a late stage of ccRCC (stage III or IV) were more likely to have high kindlin-2 expression levels than those at an early stage (stage I or II) (χ(2) = 4.72, P = 0.03). Patients with high levels of kindlin-2 expression had higher risk of hematogenous metastasis (χ(2) = 6.70, P = 0.01) than those with low levels of kindlin-2 expression. In addition, the survival time was significantly shorter for patients with high levels of kindlin-2 expression than for those with low levels of kindlin-2 expression (P = 0.001 for overall survival [OS] and P = 0.002 for disease-free survival [DFS]). Multivariate survival analysis based on the Cox proportional hazards model showed that high kindlin-2 expression levels had a hazard risk (HR) of 1.76 for OS (95% CI 1.19-2.62, P = 0.005) and an HR of 1.47 for DFS (95% CI = 1.05-2.06, P = 0.026). By comparison, lymph node metastasis had an HR of 1.48 for OS (95% CI 1.04-2.10, P = 0.029) and an HR of 1.41 for DFS (95% CI 1.04-1.93, P = 0.029). This study provided strong evidence that increased kindlin-2 expression might be involved in promoting tumor invasiveness and leading to a poor prognosis of ccRCC.

Spinal cord injury in rats treated using bone marrow mesenchymal stem-cell transplantation.

The aim of this study was to observe the effects of bone marrow mesenchymal stem-cell transplantation (BMSCs) in repairing acute spinal cord damage in rats and to examine the potential beneficial effects. 192 Wistar rats were randomized into 8 groups. Spinal cord injury was created. Behavior and limb functions were scored. Repairing effects of BMSCs transplantation was evaluated and compared. In vitro 4',6-diamidino-2-phenylindole (DAPI)-tagged BMSCs were observed, and whether they migrated to the area of spinal cord injury after intravenous tail injection was investigated. The expression of neuron-specific protein (NSE) on BMSCs was examined. Fifteen days after transplantation, the BMSCs-treated groups scored significantly higher in limb function tests than the untreated group. Pathological sections of the bone marrow after operation showed significant recovery in treated groups in comparison to the control group. After transplantation, small amounts of fluorescent-tagged BMSCs can be found in the blood vessels in the area of spinal cord injury, and fluorescent-tagged BMSCs were diffused in extravascular tissues, whereas the DAPI-tagged BMSCs could not be detected,and BrdU/NSE double-labeled cells were found in the injured marrow. BMSCs improve behavioral responses and can repair spinal cord injuries by migrating to the injured area, where they can differentiate into neurons.

Circulating antibodies to p16 protein-derived peptides in breast cancer.

Overexpression of the p16 protein has been reported in breast cancer and may trigger the secretion of antibodies against itself. Circulating anti-p16 antibodies that were detected with a recombinant protein have been reported in breast cancer. The present study was designed to determine whether the levels of circulating IgG antibody to p16 protein-derived linear antigens are altered in breast cancer. An enzyme-linked immunosorbent assay (ELISA) was developed in-house to determine circulating IgG against peptide antigens derived from the p16 protein in 152 female breast cancer patients and 160 healthy female subjects. The Student's T-test revealed that breast cancer patients exhibited significantly higher levels of anti-p16 IgG antibody compared to control subjects (T=2.02, P=0.045). In addition, ductal cancer appeared to be the main type contributing to the increased levels of circulating anti-p16 antibodies (T=2.08, P=0.038). Of all four stages of breast cancer, stage I was associated with the highest levels of IgG antibody (T=2.02, P=0.045) and receiver operating characteristic (ROC) analysis demonstrated that the area under the ROC curve was 0.74 (95% confidence interval: 0.65-083) and that the sensitivity against a specificity of 90% was 30.3%. Therefore, the levels of circulating IgG antibody to the p16 protein may be a potential biomarker for early diagnosis of breast cancer.